多肽、蛋白质药物的聚乳酸及其共聚物微球研究进展

综述了以可生物降解的合成高分子材料-聚乳酸及其共聚物为载体的多肽，蛋白质药物微球的制备方法和影响因素。讨论了蛋白质在制备和释放过程中的稳定性。     

替莫唑胺聚乳酸-羟基醋酸微球的制备及体外释药

目的:对替莫唑胺聚乳酸-羟基醋酸微球的制备工艺、含量测定及体外释药特性进行初步研究。方法:以人工合成可生物降解聚合物聚乳酸-羟基醋酸为载体,采用乳化-溶剂挥发法制备替莫唑胺聚乳酸-羟基醋酸微球,用紫外分光光度计测定其药物含量和体外释药量。结果:所制备的替莫唑胺聚乳酸-羟基醋酸微球外形圆整,算术平均球径为62.2μm,载药量为7.47%,包封率为83.53%,体外释放可达1个月。结论:替莫唑胺聚乳酸-羟基醋酸微球具有很好的控释能力,使用前景广阔。     

聚乳酸、聚乳酸乙醇酸共聚物微球的制备及影响其质量因素的研究进展

本文综述了近年来以聚乳酸、聚乳酸乙醇酸共聚物为载体的微示的研究进展,并介绍此类微球的制备方法及影响其质量的主要因素。研究表明,载体和药物的性质及微球的制备工艺等对微球的质量和体外释放等均有重要的影响。     

阿霉素聚乳酸微球的制备及体外释药特性研究

目的:对阿霉素聚乳酸微球的制备工艺、含量测定及体外释药特性进行初步研究.方法:以人工合成可生物降解聚合物聚乳酸为载体,采用乳化-溶剂挥发法制备阿霉素聚乳酸微球,用UV-260紫外分光光度计测定其药物含量和体外释药量.结果:所制备的阿霉素聚乳酸微球外形圆整,算术平均球径为55.2 μm,载药量为30.21 μg*mg-1,12 h体外累积释药量36%.结论:聚乳酸微球具有很好的控释能力,使用前景广阔.     

蛋白质/多肽药物聚乳酸/乳酸-羟基乙酸共聚物微球研究进展

缓释微粒给药系统是蛋白质/多肽药物传输系统的一个重要研究方向，聚乳酸和乳酸-羟基乙酸共聚物是制备缓释微球最常用的载体材料。蛋白质/多肽药物聚乳酸/乳酸-羟基乙酸共聚物微球常用的制备方法包括溶剂萃取/挥发法(复乳法)、相分离法和喷雾干燥法。本文总结了微球制备中面临的难点如蛋白质/多肽药物稳定性、包封率、药物突释和药物吸附等问题，并综述了保持药物结构稳定性和生物活性、提高包封率、改善药物释放曲线等微球制备方法和进展。     

聚乳酸载药微球的制备及修饰研究进展

聚乳酸(PLA)是一种新型的高分子聚合物,不溶于水、乙醇,可溶于二氯甲烷(DCM)、丙酮等.PLA无免疫原性,它以玉米为主要原料,合成及改性技术已经趋于成熟[1].PLA和乳酸-羟基乙酸共聚物(PLGA)都具有良好的生物相容性,在体内最终代谢为二氧化碳和水,是可用于人体的生物降解材料.PLA有良好的力学性能[2],也有亲水性不足等缺点,为改善药物的靶向性及释药速度,常需要对其进行修饰.与其他靶向释药系统相比,微球具有制备较简单、稳定性好、成本低等特点,为近年来研究的热点[3].不过有些PLA微球的包封率和载药量低,突释及体内生物降解而造成药物难以在最恰当的时间内释放,以至于有些制剂尚难以应用于临床.本文从制备和修饰方面综述近几年PLA微球的研究进展.     

聚乳酸微球体外降解研究(英文)

本文研究了聚乳酸微球降解的规律及机理。用五种方法研究聚乳酸微球降解过程：扫描电子显微镜观察微球表面形态;测定失重;凝胶渗透色谱法测定聚合物的平均相对分子质量;测定pH;紫外分光光度法测定乳酸含量。聚乳酸微球的降解过程有两个阶段,初期主要发生聚合物分子链断裂和相对分子质量减小,后期主要发生聚合物片段溶蚀和重量减少。其降解速度随平均相对分子质量增加而减慢。聚乳酸是可生物降解材料,降解有规律,是优良的药物控制释放材料。     

聚乳酸羟基乙酸载药微球的研究进展

综述聚乳酸羟基乙酸(PLGA)载药微球的制备方法及其微球中药物释放的研究。     

PLGA微球的修饰及其应用

微球作为新型的药物载体系统已广泛用于临床研究,高分子化合物材料聚乳酸-羟基乙酸(pdy lactic-co-glycolic acid,PLGA)因其良好的生物相容性和生物可降解性备受关注。近年来,PLGA微球的研究一直是热门,针对其释放缺陷出现了很多复合修饰方法,主要包括环糊精、壳聚糖、聚乳酸、明胶、泊洛沙姆、聚乙烯亚胺等高分子材料的联用、针对末端基团进行化学修饰以及制备成核壳型微球,在保证包封率的情况下大大降低突释,改善药物释放曲线,从而在药物传递、基因治疗、影像诊断、组织工程等领域得到了广泛的应用。     

微球给药系统研究进展

微球(microsphere)是指药物溶解或者分散在高分子材料基质中形成的微小球状实体,常见粒径在1—40μm之间,属于基质型骨架微粒。微球用于药物载体的研究始于20世纪70年代中期,发展十分迅速。药物制成微球后,因其对特定器官和组织的靶向性及微粒中药物释放的缓释性,已经成为近年来缓控释剂型研究的热点。微球根据材料可分为生物降解型、非生物降解型;根据临床用途可分为非靶向制剂和靶向制剂^[1]。     

不同PLGA型号对奥曲肽微球的包封率和体外释放行为的影响

考察了不同型号聚乳酸-羟基乙酸共聚物(PLGA)作为水溶性药物奥曲肽微球载体对载药量、包封率和体外释放行为的影响.结果表明,PLGA中丙交酯含量降低,载药量和包封率降低,而突释量增大.PLGA型号相同时,黏度较大的PLGA微球载药量和包封率较高,突释量较小.采用PLGA与聚乳酸(PLA)混合材料制备的微球比单用PLGA材料微球的突释量小、载药量和包封率高、缓释效果好.     

Biodegradable microspheres of ketorolac tromethamine for parenteral administration

Ketorolac tromethamine loaded microspheres were prepared using two different polyesters, namely poly (lactic acid) and poly (glycolic acid) by solvent evaporation technique. The morphology of microspheres was analysed by scanning electron microscopy. In vitro release profiles of these microspheres were studied in phosphate buffered saline pH 7.4. The release kinetics of ketorolac tromethamine from the microspheres was evaluated by fitting the release data to the zero-order, Higuchi and korsemeyer-peppas equations. All microspheres showed initial burst release, followed by fickian diffusion of drug through microspheres. These microspheres were formulated as parenterals to have controlled release system.     

生物可降解型石杉碱甲微球的研究

目的制备能够在一个月甚至更长时间内缓释石杉碱甲的注射型生物可降解微球。方法选用端基不封口的PLA或PLGA、采用简单的O/W乳化溶剂挥发法制备微球;详细考察了微球的形态、粒径及分布、载药量和包封率;用透析法测定微球的体外药物释放曲线。结果成功地将石杉碱甲包裹入聚合物中;制得的微球表面光滑,但不同材料制得的微球内部结构不同,粒径全部小于250μm,粒径分布较窄,载药量的质量分数在4%~6.5%内,包封率的质量分数在45%-65%内,比用端基封口的聚合物制备的微球包封率高15倍以上;体外释药试验表明,载有石杉碱甲的3种微球能够在5-7周内缓释药物。结论利用生物可降解型微球缓释石杉碱甲是可行的。     

布比卡因缓释微球的制备及体外释药特性评价

目的研究布比卡因缓释微球制备方法并对其体外释药特性进行评价。方法采用紫外分光光度法测定布比卡因微球载药量、包封率;采用HPLC法测定微球体外释放;通过正交设计优选微球制备工艺;以乳酸羟基乙酸共聚物为载体,使用乳化溶剂挥发法制备布比卡因微球;用扫描电镜观察所得微球的粒径和形态;通过体外释药实验考察布比卡因乳酸羟基乙酸共聚物微球的缓释作用。结果微球载药量、包封率和体外释放的测定方法符合方法学要求;按照优选处方制备所得的微球为圆整球体,表面多孔,呈蜂窝状,粒径50~100μm之间的微球占80%;体外释放符合Ritger-Peppas方程,t1/2=242.05 h。结论乳化溶剂挥发法适用于布比卡因乳酸羟基乙酸共聚物微球的制备,所制得的微球形态圆整,在体外具有明显缓释作用。     

Biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres for sustained release of risperidone: Zero-order release formulation

The preparation and investigation of sustained-release risperidone-encapsulated microspheres using erodible poly(D, L-lactide-co-glycolide) (PLGA) of lower molecular weight were performed and compared to that of commercial Risperdal Consta^? for the treatment of schizophrenia. The research included screening and optimizing of suitable commercial polymers of lower molecular weight PLGA50/50 or the blends of these PLGA polymers to prepare microspheres with zero-order release kinetics properties. Solvent evaporation method was applied here while studies of the risperidone loaded microsphere were carried out on its drug encapsulation capacity, morphology, particle size, as well as in vitro release profiles. Results showed that microspheres prepared using 50504A PLGA or blends of 5050-type PLGAs exerted spherical and smooth morphology, with a higher encapsulation efficiency and nearly zero-order release kinetics. These optimized microspheres showed great potential for a better depot preparation than the marketed Risperdal Consta^?, which could further improve the patient compliance.     

重组降血压肽缓释微球的制备与体外释放

目的采用复乳溶剂蒸发法制备重组降血压肽(rAHP)缓释微球。方法以聚乳酸(PLA)为缓释材料,利用正交设计优化微球制备的最佳工艺条件,并考察了微球的体外释药特性。结果微球制备的最优工艺为:油相中PLA的浓度为7.5%、初乳搅拌速度为900 r/min、内水相与油相体积比为1∶10,外水相聚乙烯醇124浓度为5%;按此工艺制备的微球粒径跨度小、分布均匀,包封率为81.35%,载药量在10.92%,微球得率在80.26%,微球的平均粒径分布范围在75～80μm之间;载药微球在磷酸盐缓冲液中0.5 h内的累积释药量为17.5%,第15天累积释药率达到98.6%。结论该微球制备工艺成熟,包封率高,符合我国药典对缓释制剂的指导原则要求。     

超微粒制备系统制备利培酮长效注射微球

目的:制备利培酮长效注射微球并进行体外释药动力学考察。方法:选用聚乳酸-羟基乙酸共聚物[poly(D,L-lactic-co-glycolic acid),PLGA]为载体,采用新型超微粒制备系统制备利培酮PLGA微球。以转碟上聚合物析出量、丝状物的形成和微粒表面形态为考察指标单因素实验优化制备工艺参数及处方;观察微球表面形态,测定其粒径、包封率、考察其体外释药动力学。结果:20%和30%载药量的微球表面均光滑圆整,分散性好;其包封率分别为94.7%和93.94%,中值粒径分别为31.65和28.13μm;持续释药时间均可达16 d,释放数据用释放动力学方程拟合符合一级和Higuchi方程。20%载药量微球1 h释药率仅为4.2%,突释率低,且其释放速率和释放时间与市售利醅酮微球(恒德)快速释放期基本一致而无延滞期。结论:超微粒制备系统(UPPS)可单步骤制备长效微球,工艺稳定,简单可行,有望成为一种适合工业微球制备技术。UPPS制备的20%载药量微球可开发为释放2周的制剂,由于无释放延滞期,将比市售品更具临床优势。     

A Heterogeneously Structured Composite Based on Poly(lactic-co-glycolic acid) Microspheres and Poly(vinyl alcohol) Hydrogel Nanoparticles for Long-Term Protein Drug Delivery

Purpose. To prepare a heterogeneously structured composite based on poly (lactic-co-glycolic acid) (PLGA) microspheres and poly(vinyl alcohol) (PVA) hydrogel nanoparticles for long-term protein drug delivery. Methods. A heterogeneously structured composite in the form of PLGA microspheres containing PVA nanoparticles was prepared and named as PLGA-PVA composite microspheres. A model protein drug, bovine serum albumin (BSA), was encapsulated in the PVA nanoparticles first. The BSA-containing PVA nanoparticles was then loaded in the PLGA microspheres by using a phase separation method. The protein-containing PLGA-PVA composite microspheres were characterized with regard to morphology, size and size distribution, BSA loading efficiency, in vitroBSA release, and BSA stability. Results. The protein-containing PLGA-PVA composite microspheres possessed spherical shape and nonporous surface. The PLGA-PVA composite microspheres had normal or Gaussian size distribution. The particle size ranged from 71.5 m to 282.7 m. The average diameter of the composite microspheres was 180 m. The PLGA-PVA composite microspheres could release the protein (BSA) for two months. The protein stability study showed that BSA was protected during the composite microsphere preparation and stabilized inside the PLGA-PVA composite microspheres. Conclusions. The protein-containing PLGA-PVA composite may be suitable for long-term protein drug delivery.     

Controlled Delivery Systems for Proteins Based on Poly(Lactic/Glycolic Acid) Microspheres

This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled horseradish peroxidase, were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 55–95 µm and encapsulated more than 90% of the protein. The preparation method was gentle and maintained enzyme activity and protein solubility. Stability studies showed that the encapsulation of an enzyme inside PLGA microspheres can protect them from activity loss. When not placed inside PLGA microspheres, (fluorescein isothiocyanate)-labeled horseradish peroxidase lost 80% of its activity in solution at 37°C in a few days, whereas inside the PLGA microspheres it retained more than 55% of its activity after 21 days of incubation at 37°C. In vitro release studies revealed that different release profiles (i.e., near-constant or biphasic) and release rates can be achieved by simply modifying factors in the preparation procedure such as mixing rate and volume of inner water and organic phases. Degradation studies by scanning electron microscopy and gel-permeation chromatography suggested that the mechanism responsible for protein release is mainly through matrix erosion.